Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Institutional glocal branding strategies with a special focus on : emerging markets.

The purpose of this dissertation is to analyse the advantages for companies to use a glocal branding strategy for their well-established institutional brands. The theoretical analysis is based on David Aaker's models of branding and on articles, journals and books covering the internationalisation of brands.Master of Business Administratio

Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy.

The utrophin-dystrophin deficient (DKO) mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD). However, it is unclear as to what extent muscle pathology affects metabolism. Therefore, the present study was focused on understanding energy expenditure in the whole animal and in isolated extensor digitorum longus (EDL) muscle and to determine changes in metabolic enzymes. Our results show that the 8 week-old DKO mice consume higher oxygen relative to activity levels. Interestingly the EDL muscle from DKO mouse consumes higher oxygen per unit integral force, generates less force and performs better in the presence of pyruvate thus mimicking a slow twitch muscle. We also found that the expression of hexokinase 1 and pyruvate kinase M2 was upregulated several fold suggesting increased glycolytic flux. Additionally, there is a dramatic increase in dynamin-related protein 1 (Drp 1) and mitofusin 2 protein levels suggesting increased mitochondrial fission and fusion, a feature associated with increased energy demand and altered mitochondrial dynamics. Collectively our studies point out that the dystrophic disease has caused significant changes in muscle metabolism. To meet the increased energetic demand, upregulation of metabolic enzymes and regulators of mitochondrial fusion and fission is observed in the dystrophic muscle. A better understanding of the metabolic demands and the accompanied alterations in the dystrophic muscle can help us design improved intervention therapies along with existing drug treatments for the DMD patients

IKKα and alternative NF-κB regulate PGC-1β to promote oxidative muscle metabolism

Although the physiological basis of canonical or classical IκB kinase β (IKKβ)-nuclear factor κB (NF-κB) signaling pathway is well established, how alternative NF-κB signaling functions beyond its role in lymphoid development remains unclear. In particular, alternative NF-κB signaling has been linked with cellular metabolism, but this relationship is poorly understood. In this study, we show that mice deleted for the alternative NF-κB components IKKα or RelB have reduced mitochondrial content and function. Conversely, expressing alternative, but not classical, NF-κB pathway components in skeletal muscle stimulates mitochondrial biogenesis and specifies slow twitch fibers, suggesting that oxidative metabolism in muscle is selectively controlled by the alternative pathway. The alternative NF-κB pathway mediates this specificity by direct transcriptional activation of the mitochondrial regulator PPAR-γ coactivator 1β (PGC-1β) but not PGC-1α. Regulation of PGC-1β by IKKα/RelB also is mammalian target of rapamycin (mTOR) dependent, highlighting a cross talk between mTOR and NF-κB in muscle metabolism. Together, these data provide insight on PGC-1β regulation during skeletal myogenesis and reveal a unique function of alternative NF-κB signaling in promoting an oxidative metabolic phenotype

Increased potentiation of force by pyruvate in DKO EDL.

<p>A). Effect of substrate on force production showing an increase in force production using pyruvate as a substrate at lower frequencies in DKO mice. B) B) Specific force produced by WT EDL is significantly higher (p<0.05) than DKO EDL when glucose is used as a substrate at 50 Hz. In the presence of pyruvate the specific force produced by WT EDL is not significantly different from DKO EDL at 50Hz. There is a significant increase in force production in DKO EDL when pyruvate is used as a substrate compared to glucose (p<0.05). However, the force produced by WT EDL in the presence of pyruvate is not significantly different from the force produced in presence of glucose. C) % Increase in force using pyruvate as a substrate relative to glucose is significantly higher in DKO EDL compared to WT at 30Hz (p = 0.0033) and D) 50Hz (p = 0.0011). p< 0.05 is significant. * = p<0.05, ** = p<0.01.</p

DKO mice weigh less but consume similar amount of food when compared to WT controls.

<p>A) DKO mice weigh significantly less than WT (p = 0.0298). B) Food consumption between WT and DKO mice is not significantly different.</p

Transmission electron microscopic images show mitochondrial localization is altered in DKO EDL muscle.

<p>A) WT EDL B) DKO EDL at 14000X magnification. C) WT and D) DKO at 34000x magnification. The arrows point to the localization of mitochondria (M) which are at the I band on either side of the Z disc in WT, but this tight localization is reduced in the DKO EDL.</p

Increased oxygen consumption relative to integral force.

<p>A) The fatigue profile of WT and DKO EDL during the 10 minutes fatigue shows that DKO EDL generates lesser force and fatigues less. B) The % of initial force after the 10 minute fatigue is higher in DKO EDL indicating less fatigue (p = 0.0019). C) The quantified force time integral over the entire 10 minutes fatigue protocol is significantly reduced in the DKO EDL compared to WT (p = 0.0097). D) Oxygen consumption over 10 minutes fatigue is not significantly different in WT and DKO EDL muscle. E). Oxygen consumed per unit integral force produced is significantly higher in DKO EDL compared to WT (p = 0.0110). p< 0.05 is significant. * = p<0.05, ** = p<0.01.</p

Whole body energy expenditure of WT and DKO mice.

<p>A) Rate of oxygen consumption in DKO mice is not significantly different from WT at both night and B) day. Respiratory exchange ratio (F) is similar in WT and DKO mice both at C) night and D) day. Activity counts measured in WT and DKO mice during E) night and F) day. Activity counts are significantly reduced (p = 0.0060) in DKO mice at night compared to WT. Oxygen consumption per unit activity is significantly higher in the DKO mice both during G) night (p = 0.0023) and H) day (p = 0.0463) p<0.05 = significant. * = p<0.05, ** = p<.01.</p